Evaluation of the Epidoxorubicin–Formaldehyde Conjugate, Epidoxoform, in a Mouse Mammary Carcinoma Model

Abstract

This study was conducted to evaluate the toxicity and efficacy of Epidoxoform, a prodrug of the active metabolite of epidoxorubicin, in a mouse model of mammary carcinoma. A dose escalation trial established a maximal tolerated dose of 20 mg/kg given intraperitoneally (IP) to 6–8 week old female C3 HeJ mice. Two days following injection of 10⁶ Gollin-B mouse mammary tumor cells into the mammary fat pad, Epidoxoform was given and tumor growth compared to mice treated similarly with the maximum tolerated dose of epidoxorubicin and untreated controls. In all efficacy trials, a significant difference was found for tumor volume between Epidoxoform and epidoxorubicin treated mice and controls. In mice treated with a two-dose regimen, significantly increased efficacy was also found between Epidoxoform compared to epidoxorubicin. Epidoxoform appears to be efficacious in this model of mammary carcinoma, with improved efficacy over the parent compound epidoxorubicin. Further evaluation of this analogue appears warranted.